RheumNow Podcast – COVID-19 Responds to Steroids (7.24.20) Save
Dr. Jack Cush Reviews the News and Journal Reports from the past week on RheumNow.com
Transcription
It's the 07/24/2020. This is the RheumNow podcast. Hi, I'm doctor Jack Cush, executive editor of roomnow.com. We are where in COVID? It's been roughly about a hundred and thirty days since this whole thing went down.
Where are you in this whole scenario? By now, this has either destroyed you, made you stronger, made you better. You've either developed new habits and new skills, or you're floundering. I'd like to know what you're doing. At the end of the podcast, I'll tell you maybe how you can tell me.
So let's start with an analysis of psoriasis versus psoriatic arthritis. This is a study by Joe Marola and colleagues that actually looked at three thousand two hundred psoriatic patients, and sought to see what the impact of their skin versus their joint was. In this analysis, nearly two thirds of the patients had both skin and joint involvement, and then there were patients who just had skin. Basically, when they in their analysis, they found that those who had both skin and joints, psoriasis and psoriatic arthritis, they had worse disease. They had a significant disease burden.
Overall, they had worse quality of life, they had more work impairment, they had higher tender joint counts, five versus two, swollen joint counts, five versus one and a half, they had more flares in a year's follow-up thirty five percent versus twenty three percent. And overall, when these people were asked, which is the bigger burden as far as disease burden on the patient, sixty two percent that said that the joints were the bigger burden versus thirty eight percent with the skin. I'm sure that the skin is a gigantic disease burden to the patient. They have a significantly higher rate of depression and suicides in psoriasis, more so than we've seen in rheumatology. And the skin is a constant reminder, but so is the joint.
And I think that both are really serious when it comes to managing psoriatic disease. A few regulatory announcements this week. The FDA issued a draft guidance paper for those of you who do research and develop drugs. This one on a hot topic, and that is cannabis and cannabis derived compounds, and what the FDA thinks about how the clinical research should be conducted, and, and some of the pitfalls and benefits of doing such research. The FDA also this week granted, a priority review for voclosporin.
This is Aurinia's calcineurin inhibitor being developed for lupus nephritis. Voclosporin has been proven in a phase two and recently phase three study that we reported at EULAR to be highly effective in lupus nephritis patients. So it will be interesting to see how that looks when it goes up in front of the FDA for review. An interesting analysis gave you an overview of what statin associated myopathy looks like. This is a 100 patients who were looked at.
The mean age at presentation was 65 years of age, they're old. They have, as do the other myopathies, proximal weakness, or sometimes with myalgias. CK is, the mean CK was 6,500, and all the patients were HMG CoA reductase antibody positive. When they did have biopsies, which was the most of the patients, actually it was about half the patients, about eighty percent of them had evidence of necrotizing myopathy. And overall, about eighty percent of these patients went on to require immunosuppressive therapy.
I must say, I've considered this diagnosis a few times, have yet to see it, although I'm looking for it, maybe you've seen it, but it's a relatively rare phenomenon amongst, all the patients who are on statins. This is a relatively rare event. So an interesting overview looked at the use of TNF inhibitors with liver disease. And in this, just sort of literature analysis by the authors, they suggested that it looks like TNF inhibitors are safe to use in patients who have nonalcoholic fatty liver disease. And that's encouraging because fatty liver is a gigantic problem amongst our patients.
And there is a rare, rare risk of hepatotoxicity with TNF inhibitors, especially with infliximab. But yet this data looks pretty good when using it in NF ALD. However, because of a lack of data and conflicting data, its use in patients who have documented cirrhosis is a little less certain and a little more speculative. No outright dangers, but really no outright benefits. So, the point being, be cautious there, maybe get the hepatologist involved in the care of such patients.
An interesting analysis looked at Still's disease patients who had lung disease. Now, they can get an interstitial lung disease, a pneumonitis, they can get pleuritis, anywhere from twenty to forty percent of the time with Still's disease. And there are rare events of serious lung disease. As you know, kids with systemic JIA have this rare complication of a progressive and really morbid outcome, lung disease. So this particular analysis was trying to look at sort of the same data.
A cohort, this is an Italian cohort of one hundred and forty seven adult onset Still's disease patients found that twelve percent, twelve percent of them had lung disease of one sort or another. If you looked at the Still's patients with lung disease, they were more likely to be older, have myalgias, lymphadenopathy, pleuritis, abdominal pain, they tend to have higher systemic disease scores, higher ferritin levels, and more mortality in this cohort with a thirty nine percent mortality in those with lung disease versus only a ten percent mortality in those without lung disease. Now, I got a problem with some of this data. I like most of what I've just told you, but the mortality, adult onset Still's disease doesn't kill anybody in my opinion. Yes, there are a few cases and whatnot, but generally, this is a highly inflammatory disorder.
It shouldn't kill anyone unless they get macrophage activation syndrome or unless they have complications of steroid therapy. Can they die from lung disease? There are reports. I think this Italian experience is a little overstating that, but let's look at it when you're seeing your patients with Still's disease. Corona put out an interesting analysis of enthesitis in their ankylosing spondylitis.
Actually their axial spondyloarthritis patients, four seventy seven were reviewed showing the twenty five percent of them had evidence of enthesitis affecting about four sites per patient at enrollment. Those with enthesitis were more likely to have surprisingly non radiographic axial SPA. They were more likely to be on biologics or DMARDs and overall, they had more disease activity as measured by tender joint count, swollen joint count, ASAS and BASDAI scores. I guess the point being, if you don't have the classic findings, you gotta have more activity findings and more disease to be classified as an axSpA, in this case, mostly non radiographic axial SpA. Enthusitis can be a problematic feature in managing patients with spondyloarthritis.
Another analysis looked at COVID this week, looking specifically at the risk of, pulmonary embolism and thrombotic events. One third of patients hospitalized with COVID, have evidence in this particular study of pulmonary embolism by CT scan. This is based on analysis of fourteen seventy seven hospitalized COVID patients, and it suggested that the highest yield for CT, for pulmonary embolism was by chest CT, and also by fine and suggested by having high D dimer levels. There's a really interesting report about Kawasaki syndrome associated with COVID nineteen. There's a number of them in the literature.
Last week's New England Journal had a feature on it. John Hausman has a paper on this also describing their experience in, at Harvard. This particular report is one case, but it happens to be in an adult, not in kids. So the one case is a 45 year old male who had Kawasaki's like manifestations presented with a six day history of fever, sore throat, diarrhea, lymphadenopathy, lower extremity pain, conjunctivitis, tachycardia, very high SED rate, extremely high CRP five forty six milligrams per liter, high troponin levels, and the patient resolved and responded very well to high dose IVIG and tocilizumab. So the authors presented this as an adult case of the same pediatric syndrome that's been making the rounds in the literature of late.
Ankle losing spondylitis also looked at by a Korean center that looked at their experience when they used, TNF inhibitors. So amongst our twelve eighty patients with ankylosing spondylitis, nearly six hundred of them were exposed to TNF inhibitors, and they showed a significant reduction in X-ray change over time, mainly we're talking about SI changes measured by the the MSAS or the what's that? I'm not even gonna try. The modified spondylitis, I don't know, MSAS, developed by Walter Meksimovich and others, a really good measure of X-ray outcomes in ankylosing spondylitis. But, you know, there are not a lot of reports that actually show that effective therapy does reduce X-ray progression in ankylosing spondylitis.
That's why I posted this one. There's some evidence here. A really interesting study comes from patients who don't have RA but might could. In this particular study, they drew upon patients from the, a UK Twin study where they actually had microbiome information along with genotyping. And they basically showed that, in patients who would ultimately go on to develop rheumatoid arthritis, that the microbiome so showed a predominance of prevotella, which has been linked with RA in the past, being positively associated with future RA risk.
They also validated this result by studying first degree relatives of RA patients where prevotella was also associated with the development of preclinical arthritis and with HLA DR beta-one or the shared epitope, suggesting this curious link between the microbiome, and our genotype that can lead to future disease. A report that happened about a month ago that I failed to report on was a result of a rizenkizumab, doing, better than secukinumab in treating patients with cutaneous psoriasis only. There's a head to head trial of three twenty seven patients with psoriasis, plaque psoriasis, who are randomized to the IL-twenty three inhibitor, rizikizumab versus the IL-seventeen inhibitor, secukinumab. The primary endpoint was week sixteen, where rizikizumab was was non inferior to secukinumab by PASI 90. The, rizikizumab PASI 90 score was seventy four percent, the secukinumab was sixty six percent.
However, by week fifty two, rizikizumab was superior to secukinumab in PASI ninety, eighty seven percent versus fifty seven percent, thus meeting both primary endpoints in this particular study. And again, there are other studies showing IL-twenty three is, has done better than IL-seventeen in treating cutaneous psoriasis. Our last two reports concerned COVID nineteen, severe COVID nineteen treated with steroids. As you know, last week, the last Thursday, a week ago last Thursday, the New England Journal reported on the recovery trial. This was a study of dexamethasone in patients who had severe COVID-nineteen and overall, that what they showed was dexamethasone, compared to, controls was, better at lowering the twenty eight day mortality, and the need for respiratory, support.
In this particular study, there was two thousand patients who were, given dexamethasone and four thousand three hundred patients who received usual care. Death rates at day twenty eight was twenty three percent versus twenty seven, twenty six percent lower in dexamethasone. Those that are required mechanical ventilation, was, dexamethasone, twenty nine percent versus forty one percent with usual care, same thing for oxygenation. The interesting thing about this study was this the benefit of dexamethasone was only seen in patients who had severe disease. Those who did not require mechanical ventilation at the outset, did not have impending respiratory failure, didn't do, any better if they were given dexamethasone in the recovery trial.
The other trial which appeared this week, I think it was in Annals Rheumatic Disease, Robert Landaway's group reported on the use of steroids in the cytokine storm syndrome. In their particular, registry, they they define cytokine storm as patients who had evidence of rapid respiratory deterioration and at least two biomarkers suggestive of cytokine storm, CRP greater than 10 milligrams per deciliter, ferritin is greater than 900, d dimer is greater than 1,500. They compared eighty six patients who were treated with high dose steroids and with or without tocilizumab to eighty six patients who were historic controls treated in roughly the same time. Half the patients received high dose steroids also went on to receive tocilizumab. And in their study, they had they were more, they had faster recovery.
There was 1.79 was the hazard ratio. They had less mortality with a hazard ratio of 0.35, 65% less. And they had less of a need for mechanical ventilation with hazard ratio of zero point two nine or seventy one percent less. Two studies clearly showing that in patients who are severe with COVID in the hospital, break out the steroids and in this case, it's not too bad to add in tocilizumab to the regimen. These are, I think, important advances in the management of the coronavirus, especially those who are really sick.
That's it for this week. You know what? Next week, we're going to start taking calls from you, the viewer. So if you want to actually ask a question that would be answered here on the podcast, go to the website, look for our podcast question feature, click on it, and you can record your question right there. And if I like it, I'll feature it on our next podcast along with maybe a few of your other colleagues' questions.
Again, I'd like to maybe even hear your comments about, you know, the reasons that you're doing great in the COVID era or maybe not doing so great. But look for that feature on the website. Again, podcast questions and a big question mark. It'll be on the homepage, and you can find it there. Go to the website, you can find these citations to read more about these important advances in rheumatology.
Hope you're doing well. Stay safe. Wear your mask. LTF, listen to Fauci.
Where are you in this whole scenario? By now, this has either destroyed you, made you stronger, made you better. You've either developed new habits and new skills, or you're floundering. I'd like to know what you're doing. At the end of the podcast, I'll tell you maybe how you can tell me.
So let's start with an analysis of psoriasis versus psoriatic arthritis. This is a study by Joe Marola and colleagues that actually looked at three thousand two hundred psoriatic patients, and sought to see what the impact of their skin versus their joint was. In this analysis, nearly two thirds of the patients had both skin and joint involvement, and then there were patients who just had skin. Basically, when they in their analysis, they found that those who had both skin and joints, psoriasis and psoriatic arthritis, they had worse disease. They had a significant disease burden.
Overall, they had worse quality of life, they had more work impairment, they had higher tender joint counts, five versus two, swollen joint counts, five versus one and a half, they had more flares in a year's follow-up thirty five percent versus twenty three percent. And overall, when these people were asked, which is the bigger burden as far as disease burden on the patient, sixty two percent that said that the joints were the bigger burden versus thirty eight percent with the skin. I'm sure that the skin is a gigantic disease burden to the patient. They have a significantly higher rate of depression and suicides in psoriasis, more so than we've seen in rheumatology. And the skin is a constant reminder, but so is the joint.
And I think that both are really serious when it comes to managing psoriatic disease. A few regulatory announcements this week. The FDA issued a draft guidance paper for those of you who do research and develop drugs. This one on a hot topic, and that is cannabis and cannabis derived compounds, and what the FDA thinks about how the clinical research should be conducted, and, and some of the pitfalls and benefits of doing such research. The FDA also this week granted, a priority review for voclosporin.
This is Aurinia's calcineurin inhibitor being developed for lupus nephritis. Voclosporin has been proven in a phase two and recently phase three study that we reported at EULAR to be highly effective in lupus nephritis patients. So it will be interesting to see how that looks when it goes up in front of the FDA for review. An interesting analysis gave you an overview of what statin associated myopathy looks like. This is a 100 patients who were looked at.
The mean age at presentation was 65 years of age, they're old. They have, as do the other myopathies, proximal weakness, or sometimes with myalgias. CK is, the mean CK was 6,500, and all the patients were HMG CoA reductase antibody positive. When they did have biopsies, which was the most of the patients, actually it was about half the patients, about eighty percent of them had evidence of necrotizing myopathy. And overall, about eighty percent of these patients went on to require immunosuppressive therapy.
I must say, I've considered this diagnosis a few times, have yet to see it, although I'm looking for it, maybe you've seen it, but it's a relatively rare phenomenon amongst, all the patients who are on statins. This is a relatively rare event. So an interesting overview looked at the use of TNF inhibitors with liver disease. And in this, just sort of literature analysis by the authors, they suggested that it looks like TNF inhibitors are safe to use in patients who have nonalcoholic fatty liver disease. And that's encouraging because fatty liver is a gigantic problem amongst our patients.
And there is a rare, rare risk of hepatotoxicity with TNF inhibitors, especially with infliximab. But yet this data looks pretty good when using it in NF ALD. However, because of a lack of data and conflicting data, its use in patients who have documented cirrhosis is a little less certain and a little more speculative. No outright dangers, but really no outright benefits. So, the point being, be cautious there, maybe get the hepatologist involved in the care of such patients.
An interesting analysis looked at Still's disease patients who had lung disease. Now, they can get an interstitial lung disease, a pneumonitis, they can get pleuritis, anywhere from twenty to forty percent of the time with Still's disease. And there are rare events of serious lung disease. As you know, kids with systemic JIA have this rare complication of a progressive and really morbid outcome, lung disease. So this particular analysis was trying to look at sort of the same data.
A cohort, this is an Italian cohort of one hundred and forty seven adult onset Still's disease patients found that twelve percent, twelve percent of them had lung disease of one sort or another. If you looked at the Still's patients with lung disease, they were more likely to be older, have myalgias, lymphadenopathy, pleuritis, abdominal pain, they tend to have higher systemic disease scores, higher ferritin levels, and more mortality in this cohort with a thirty nine percent mortality in those with lung disease versus only a ten percent mortality in those without lung disease. Now, I got a problem with some of this data. I like most of what I've just told you, but the mortality, adult onset Still's disease doesn't kill anybody in my opinion. Yes, there are a few cases and whatnot, but generally, this is a highly inflammatory disorder.
It shouldn't kill anyone unless they get macrophage activation syndrome or unless they have complications of steroid therapy. Can they die from lung disease? There are reports. I think this Italian experience is a little overstating that, but let's look at it when you're seeing your patients with Still's disease. Corona put out an interesting analysis of enthesitis in their ankylosing spondylitis.
Actually their axial spondyloarthritis patients, four seventy seven were reviewed showing the twenty five percent of them had evidence of enthesitis affecting about four sites per patient at enrollment. Those with enthesitis were more likely to have surprisingly non radiographic axial SPA. They were more likely to be on biologics or DMARDs and overall, they had more disease activity as measured by tender joint count, swollen joint count, ASAS and BASDAI scores. I guess the point being, if you don't have the classic findings, you gotta have more activity findings and more disease to be classified as an axSpA, in this case, mostly non radiographic axial SpA. Enthusitis can be a problematic feature in managing patients with spondyloarthritis.
Another analysis looked at COVID this week, looking specifically at the risk of, pulmonary embolism and thrombotic events. One third of patients hospitalized with COVID, have evidence in this particular study of pulmonary embolism by CT scan. This is based on analysis of fourteen seventy seven hospitalized COVID patients, and it suggested that the highest yield for CT, for pulmonary embolism was by chest CT, and also by fine and suggested by having high D dimer levels. There's a really interesting report about Kawasaki syndrome associated with COVID nineteen. There's a number of them in the literature.
Last week's New England Journal had a feature on it. John Hausman has a paper on this also describing their experience in, at Harvard. This particular report is one case, but it happens to be in an adult, not in kids. So the one case is a 45 year old male who had Kawasaki's like manifestations presented with a six day history of fever, sore throat, diarrhea, lymphadenopathy, lower extremity pain, conjunctivitis, tachycardia, very high SED rate, extremely high CRP five forty six milligrams per liter, high troponin levels, and the patient resolved and responded very well to high dose IVIG and tocilizumab. So the authors presented this as an adult case of the same pediatric syndrome that's been making the rounds in the literature of late.
Ankle losing spondylitis also looked at by a Korean center that looked at their experience when they used, TNF inhibitors. So amongst our twelve eighty patients with ankylosing spondylitis, nearly six hundred of them were exposed to TNF inhibitors, and they showed a significant reduction in X-ray change over time, mainly we're talking about SI changes measured by the the MSAS or the what's that? I'm not even gonna try. The modified spondylitis, I don't know, MSAS, developed by Walter Meksimovich and others, a really good measure of X-ray outcomes in ankylosing spondylitis. But, you know, there are not a lot of reports that actually show that effective therapy does reduce X-ray progression in ankylosing spondylitis.
That's why I posted this one. There's some evidence here. A really interesting study comes from patients who don't have RA but might could. In this particular study, they drew upon patients from the, a UK Twin study where they actually had microbiome information along with genotyping. And they basically showed that, in patients who would ultimately go on to develop rheumatoid arthritis, that the microbiome so showed a predominance of prevotella, which has been linked with RA in the past, being positively associated with future RA risk.
They also validated this result by studying first degree relatives of RA patients where prevotella was also associated with the development of preclinical arthritis and with HLA DR beta-one or the shared epitope, suggesting this curious link between the microbiome, and our genotype that can lead to future disease. A report that happened about a month ago that I failed to report on was a result of a rizenkizumab, doing, better than secukinumab in treating patients with cutaneous psoriasis only. There's a head to head trial of three twenty seven patients with psoriasis, plaque psoriasis, who are randomized to the IL-twenty three inhibitor, rizikizumab versus the IL-seventeen inhibitor, secukinumab. The primary endpoint was week sixteen, where rizikizumab was was non inferior to secukinumab by PASI 90. The, rizikizumab PASI 90 score was seventy four percent, the secukinumab was sixty six percent.
However, by week fifty two, rizikizumab was superior to secukinumab in PASI ninety, eighty seven percent versus fifty seven percent, thus meeting both primary endpoints in this particular study. And again, there are other studies showing IL-twenty three is, has done better than IL-seventeen in treating cutaneous psoriasis. Our last two reports concerned COVID nineteen, severe COVID nineteen treated with steroids. As you know, last week, the last Thursday, a week ago last Thursday, the New England Journal reported on the recovery trial. This was a study of dexamethasone in patients who had severe COVID-nineteen and overall, that what they showed was dexamethasone, compared to, controls was, better at lowering the twenty eight day mortality, and the need for respiratory, support.
In this particular study, there was two thousand patients who were, given dexamethasone and four thousand three hundred patients who received usual care. Death rates at day twenty eight was twenty three percent versus twenty seven, twenty six percent lower in dexamethasone. Those that are required mechanical ventilation, was, dexamethasone, twenty nine percent versus forty one percent with usual care, same thing for oxygenation. The interesting thing about this study was this the benefit of dexamethasone was only seen in patients who had severe disease. Those who did not require mechanical ventilation at the outset, did not have impending respiratory failure, didn't do, any better if they were given dexamethasone in the recovery trial.
The other trial which appeared this week, I think it was in Annals Rheumatic Disease, Robert Landaway's group reported on the use of steroids in the cytokine storm syndrome. In their particular, registry, they they define cytokine storm as patients who had evidence of rapid respiratory deterioration and at least two biomarkers suggestive of cytokine storm, CRP greater than 10 milligrams per deciliter, ferritin is greater than 900, d dimer is greater than 1,500. They compared eighty six patients who were treated with high dose steroids and with or without tocilizumab to eighty six patients who were historic controls treated in roughly the same time. Half the patients received high dose steroids also went on to receive tocilizumab. And in their study, they had they were more, they had faster recovery.
There was 1.79 was the hazard ratio. They had less mortality with a hazard ratio of 0.35, 65% less. And they had less of a need for mechanical ventilation with hazard ratio of zero point two nine or seventy one percent less. Two studies clearly showing that in patients who are severe with COVID in the hospital, break out the steroids and in this case, it's not too bad to add in tocilizumab to the regimen. These are, I think, important advances in the management of the coronavirus, especially those who are really sick.
That's it for this week. You know what? Next week, we're going to start taking calls from you, the viewer. So if you want to actually ask a question that would be answered here on the podcast, go to the website, look for our podcast question feature, click on it, and you can record your question right there. And if I like it, I'll feature it on our next podcast along with maybe a few of your other colleagues' questions.
Again, I'd like to maybe even hear your comments about, you know, the reasons that you're doing great in the COVID era or maybe not doing so great. But look for that feature on the website. Again, podcast questions and a big question mark. It'll be on the homepage, and you can find it there. Go to the website, you can find these citations to read more about these important advances in rheumatology.
Hope you're doing well. Stay safe. Wear your mask. LTF, listen to Fauci.
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